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基于前体蛋白转化酶内源性和外源性抑制剂开发新型治疗药物的潜在机会。

Potential opportunity in the development of new therapeutic agents based on endogenous and exogenous inhibitors of the proprotein convertases.

作者信息

Bontemps Yannick, Scamuffa Nathalie, Calvo Fabien, Khatib Abdel-Majid

机构信息

INSERM, U 716, Equipe AVENIR, Institut de Génétique Moléculaire, Paris 75010, France.

出版信息

Med Res Rev. 2007 Sep;27(5):631-48. doi: 10.1002/med.20072.

DOI:10.1002/med.20072
PMID:17019676
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7168524/
Abstract

The proprotein convertases (PCs) are responsible for the endoproteolytic processing of various protein precursors (e.g., growth factors, receptors, adhesion molecules, and matrix metalloproteinases) implicated in several diseases such as obesity, diabetes, atherosclerosis, cancer, and Alzheimer disease. The potential clinical and pharmacological role of the PCs has fostered the development of various PC-inhibitors. In this review we summarized the recent findings on PCs inhibitors, their mode of actions and potential use in the therapy of various diseases.

摘要

前蛋白转化酶(PCs)负责多种蛋白质前体(如生长因子、受体、黏附分子和基质金属蛋白酶)的内切蛋白水解加工,这些蛋白质前体与肥胖、糖尿病、动脉粥样硬化、癌症和阿尔茨海默病等多种疾病有关。PCs的潜在临床和药理学作用推动了各种PC抑制剂的开发。在本综述中,我们总结了关于PC抑制剂的最新研究结果、它们的作用模式以及在各种疾病治疗中的潜在用途。

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Potential opportunity in the development of new therapeutic agents based on endogenous and exogenous inhibitors of the proprotein convertases.基于前体蛋白转化酶内源性和外源性抑制剂开发新型治疗药物的潜在机会。
Med Res Rev. 2007 Sep;27(5):631-48. doi: 10.1002/med.20072.
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本文引用的文献

1
Endo/exo-proteolysis in neoplastic progression and metastasis.肿瘤进展和转移中的内/外蛋白水解作用
J Mol Med (Berl). 2005 Nov;83(11):856-64. doi: 10.1007/s00109-005-0692-y. Epub 2005 Aug 26.
2
Modulating furin activity with designed mini-PDX peptides: synthesis and in vitro kinetic evaluation.用设计的微型PDX肽调节弗林蛋白酶活性:合成及体外动力学评估
FEBS Lett. 2005 Aug 29;579(21):4813-21. doi: 10.1016/j.febslet.2005.07.062.
3
Inter-alpha-inhibitor proteins are endogenous furin inhibitors and provide protection against experimental anthrax intoxication.α-抑制剂间蛋白是内源性弗林蛋白酶抑制剂,可提供针对实验性炭疽中毒的保护作用。
Infect Immun. 2005 Aug;73(8):5101-5. doi: 10.1128/IAI.73.8.5101-5105.2005.
4
Regulation of the stepwise proteolytic cleavage and secretion of PDGF-B by the proprotein convertases.前蛋白转化酶对血小板衍生生长因子-B(PDGF-B)逐步进行蛋白水解切割及分泌的调控。
Oncogene. 2005 Oct 20;24(46):6925-35. doi: 10.1038/sj.onc.1208838.
5
Human carcinoma cell growth and invasiveness is impaired by the propeptide of the ubiquitous proprotein convertase furin.遍在的前蛋白转化酶弗林蛋白酶原肽可损害人癌细胞的生长和侵袭能力。
Cancer Res. 2005 May 15;65(10):4162-71. doi: 10.1158/0008-5472.CAN-04-2820.
6
Bordetella dermonecrotic toxin exerting toxicity through activation of the small GTPase Rho.博德特氏菌皮肤坏死毒素通过激活小GTP酶Rho发挥毒性作用。
J Biochem. 2004 Oct;136(4):415-9. doi: 10.1093/jb/mvh155.
7
Implication of proprotein convertases in the processing and spread of severe acute respiratory syndrome coronavirus.前体蛋白转化酶在严重急性呼吸综合征冠状病毒的加工和传播中的作用
Biochem Biophys Res Commun. 2005 Jan 21;326(3):554-63. doi: 10.1016/j.bbrc.2004.11.063.
8
BCL-2-induced glioma cell invasiveness depends on furin-like proteases.BCL-2诱导的胶质瘤细胞侵袭性依赖于弗林样蛋白酶。
J Neurochem. 2004 Dec;91(6):1275-83. doi: 10.1111/j.1471-4159.2004.02806.x.
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Proprotein convertase models based on the crystal structures of furin and kexin: explanation of their specificity.基于弗林蛋白酶和凯新蛋白酶晶体结构的前体蛋白转化酶模型:对其特异性的解释。
J Mol Biol. 2005 Jan 14;345(2):211-27. doi: 10.1016/j.jmb.2004.10.050.
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Rational redesign of inhibitors of furin/kexin processing proteases by electrostatic mutations.通过静电突变对弗林蛋白酶/凯新加工蛋白酶抑制剂进行合理重新设计。
Acta Pharmacol Sin. 2004 Dec;25(12):1712-818.